Chronic pain has been identified by consumers and health care providers as a significant secondary complication for persons with disabilities. The treatment of this condition is often unsatisfactory with most treatments adapted from other pain populations without adequate testing or modification. The focus of this program project is the development and evaluation of treatments for chronic pain in persons with amputations and spinal cord injuries (SCI). This program investigates interventions to treat pathophysiologic processes and impairments while reducing functional limitations, disability and handicap. Project I investigates the use of a neurotoxin, adriamycin, to treat pain secondary to neuroma formation in persons with amputations. Histopathological and electrophysiological studies in animals will determine the response of neuromas to treatment with adriamycin. These laboratory studies will lay the foundation for a clinical study in humans investigating neuroma resection with the addition of adriamycin. Project II investigates pharmacological treatments for chronic pain in persons with amputations. This project will use a double-blind, placebo-controlled, cross-over study to assess the efficacy of long acting opioids and mexiletine to ameliorate pain and improve function in persons with phantom limb pain. Project III investigates the efficacy of nortriptyline and cognitive- behavioral treatment, individually and in combination, in reducing pain and pain-related disability for persons with SCI in a randomized, placebo-controlled clinical trial. The Administrative Core will promote interaction among the interdisciplinary research team, facilitate allocation of resources and provide for internal and external review of the research program. The integration of research programs ranging from basic science to clinical trials and the interdisciplinary nature of the research team will result in greater scientific contributions than if each project were pursued individually. Particular strengths of the program project are the emphasis on potential new treatments specifically for persons with disabilities and on measuring outcomes at the levels of impairment, disability and handicap. The program project brings together, in a collaborative effort, an interdisciplinary, high productive group of basic science and clinical pain researchers to address an important problem for persons with disabilities.